Almost all humans have genetic defects hidden in cells, study shows

The arrival of fast and relatively inexpensive genome sequencing is likely to open whole new avenues for diagnosing and treating diseases.

But in a new study, scientists show that it can also reveal how some age-related diseases -- from diabetes to neurodegenerative disorders such as Parkinson's disease and dementia -- establish a foothold in the human body, and in doing so, point the way to preventing such diseases.

The latest research zeros in on mitochrodrial DNA -- the much smaller but more diverse packet of genetic material packaged not in the nucleus of a cell, but in the small cellular power plants called mitochondria, which convert energy from food into cellular fuel. Conducting detailed mitochondrial DNA scans of 1,095 healthy humans from 14 distinct populations across the globe, the researchers found that at least 1 in 5 healthy humans carry at least one disease-related mutation in their mitochondrial DNA -- a condition called heteroplasmy. And 90 percent have mitochondrial DNA mutation of some sort.

Yet they were all still healthy.

Mitochondrial DNA contains 37 genes -- a tiny fraction of the estimated 20,000 to 25,000 total genes in the human genome. But a fault in any one of those mitochondrial genes -- whether inherited or the result of spontaneous mutation -- can wreak havoc with cells across the body.

Diseases linked to defects in mitochondrial DNA can cause a wide range of debilitating and deadly conditions, affecting growth, development and the proper function of the muscles, brain and metabolism.

But the point at which heteroplasmy in mitochondrial DNA results in observable disease is unknown. Scientists have suspected that the severity of mitochondrial diseases is a function of the percentage of mitochondria that carry mutated DNA. And they have observed that older people, and people who are clearly sick with diseases of aging such as cancer, heart disease and diabetes, tend to have many more such mutations than younger, healthier folk.

But when nearly all of us seem to carry some mutations in these special genes, what's the tripping point that begins the downward spiral toward illness? And how do healthy people get from having a small number of heteroplasmies to having enough to cause the body to break down?

Those are questions still to be explored. But for now, at least, the latest research offers a glimpse of where humans start that process. Computational modeling done elsewhere has already shown that in the length of the average human's lifespan, there's enough time and cellular turnover to allow spontaneous mutations to occur and become widely prevalent in cells. But which heteroplasmies in mitochondrial DNA are worst, and what factors accelerate those mutations and their spread, all need to be explored.

Answers to such questions might point to ways to slow or block those mutations, or their expansion to cells throughout the body. And that, in turn, might nip diseases in the bud.

"Managing the expansion" of these disease-related mutations in mitochondrial DNA "could be a promising means of preventing disease progression," the authors write. Their study was published Monday in the journal PNAS.